糙海参中三萜皂苷活性成分的研究

Study on bioactive triterpene glycosides of sea cucumber Holothuria scabra Jaeger

目的:研究糙海参(HolothuriascabraJaeger)的三萜皂苷类抗癌活性成分。方法:应用大孔树脂柱层析、葡聚糖凝胶柱层析、正相硅胶柱层析、反相硅胶柱层析和HPLC进行三萜皂苷成分的分离纯化,根据化合物的理化性质和波谱数据鉴定其结构。并对提取到的化合物进行了稻瘟霉和体外细胞毒(针对MKN45人胃癌肿瘤细胞和HCT116人肠癌肿瘤细胞)的活性检测。结果:分离鉴定了5个三萜皂苷化合物,分别为24dehydroechinosideA(1),echinosideB(2),echinosideA(3),holothurinB(4)和holothurinA(5)。化合物1～5对稻瘟霉的最小活性浓度分别为<7.9、<15.7l、<7.9、<15.7、<7.9μg/ml,对MKN45人胃癌肿瘤细胞的IC50值分别为1.60、0.18、1.86、1.59、2.37μmol/L,对HCT116人肠癌肿瘤细胞的IC50值分别为1.46、3.31、1.98、1.60、0.24μmol/L。结论:化合物1为首次以原生产物形式得到的单体天然产物,2～5为首次从糙海参中分离得到。5个化合物均显示显著的体外细胞毒活性。

Objective:To study the antineoplastic triterpene glycosides of sea cucumber Holothuria scabra Jaeger. Methods: Triterpene glycosides in the sea cucumber were isolated and purified by column chromatography on DA-101 resin, silica gel, reversed-phase silica and reversed-phase HPLC. Their chemical structures were identified on the basis of chemical evidence and spectral data. The antipyricularia oryzae and antineoplastic activities of the compounds obtained were tested with MKN-45 cells and HCT-116 cells. Results: Five triterpene glycosides were obtained from the sea cucumber studied and their structures were identified as 24-dehydroechinoside A (1), echinoside B(2), echinoside A(3), holothurin B(4) and holothurin A(5). Their minimal effective concentrations for the antipyricularia oryzae were <7.9,<15.7,<7.9,<15.7 and <7.9 μg/ml,respectively; their IC 50 for MKN-45 cells were 1.60, 0.18, 1.86, 1.59 and 2.37 μmol/L,respectively;and their IC 50 for HCT-116 cells were 1.46, 3.31, 1.98, 1.60, and 0.24 μmol/L,respectively. Conclusion: Compound 1 is the original product isolated from the natural world for the first time, and the other 4 compounds are obtained from Holothuria scabra Jaeger for the first time. All glycosides show marked in vitro antineoplastic activity.